Supramolecular synthesis of coumarin derivatives catalyzed by a coordination-assembled cage in aqueous solution

A self-assembled Pd_4L_2 cage is employed as a water-soluble molecular flask for the synthesis of functionalized coumarins from a series of salicylaldehyde derivatives and cyanoacetates/malononitrile. The catalytic reaction features mild aqueous conditions and broad substrate scope. Crystal structures of the host-guest complexes for two substrates and one analogous intermediate have been obtained, shedding light on the supramolecular reaction mechanism. Michaelis-Menten kinetic studies were performed in one typical case, revealing that the rate of product formation has been enhanced by over 23-fold in contrast to the background reaction without cage. Moreover, the same reaction catalyzed by a smaller Pd_6L_4 cage gives a mixture of products and much lower yields, suggesting that fine-tuning on the size and symmetry of the cages' cavity is crucial for their applications in supramolecular catalysis.     

Chemoenzymatic synthesis of O-mannosylpeptides in solution and on solid phase

O-mannosyl glycans are known to play an important role in regulating the function of α-dystroglycan (α-DG), as defective glycosylation is associated with various phenotypes of congenital muscular dystrophy. Despite the well-established biological significance of these glycans, questions regarding their precise molecular function remain unanswered. Further biological investigation will require synthetic methods for the generation of pure samples of homogeneous glycopeptides with diverse sequences. Here we describe the first total syntheses of glycopeptides containing the tetrasaccharide NeuNAcα2-3Galβ1-4GlcNAcβ1-2Manα, which is reported to be the most abundant O-mannosyl glycan on α-DG. Our approach is based on biomimetic stepwise assembly from the reducing end and also gives access to the naturally occurring mono-, di-, and trisaccharide substructures. In addition to the total synthesis, we have developed a "one-pot" enzymatic cascade leading to the rapid synthesis of the target tetrasaccharide. Finally, solid-phase synthesis of the desired glycopeptides directly on a gold microarray platform is described.     

Zeolite catalysed synthesis of coumarin derivatives

The direct synthesis of coumarin derivatives from m-substituted phenols and α,β-unsaturated carboxylic acids catalysed by solid-acid catalysts, such as zeolite H-Beta or Amberlyst-15, in toluene as solvent was studied. The conversion involves esterification followed by alkylation (ring closure). Ring closure of the ester is promoted both by an appropriate substituent on the aromatic ring and by Michael activation of the β-carbon of the ester. These influences were studied by variation of the reactants. 7-Hydroxy-3,4-dihydrocoumarin is formed in high yield when resorcinol and propenoic acid are used as reactants.     

Combination of solid phase and solution phase synthesis of oligosaccharides using sonication

An approach that combines solid phase and solution phase synthesis of oligosaccharides via the assistance of sonication has been developed. By employing the traceless linker, the designed oligosaccharides can be obtained in pure form and, more importantly, ready for incorporation to aglycons of interest via ‘Click’ chemistry or amide linkage. The overall strategy will facilitate the studies of roles of carbohydrates in bioactive compounds.     

A novel synthesis of coumarin derivatives

The chemical behaviors of 3-ethynylcoumarin towards benzyl bromide,diazonium chic ride,hydrogen chloride,ethyl magnesium bromide and its self-coupling are reported.     

Design and synthesis of fluorogenic substrates that target protein phosphatases

We have successfully designed and synthesized new fluorogenic probes that specifically target different classes of protein phosphatases. The fluorescence profiles of the probes have been studied using 12 different phosphatases, and results showed that, besides alkaline and tyrosine phosphatases, our probes were able to detect serine/threonine as well as acid phosphatases.     

Divergent behavior of glycosylated threonine and serine derivatives in solid phase Peptide synthesis

Solid phase peptide coupling of glycosylated threonine derivatives was systematically evaluated. In contrast to glycosylated serine derivatives which are highly prone to epimerization, glycosylated threonine derivatives produce only negligible amounts of epimerization. Under forcing conditions, glycosylated threonine analogs undergo β-elimination, rather than epimerization. Mechanistic studies and molecular modeling were used to understand the origin of the differences in reactivity.     

Rational design and synthesis of 3-heteroaromatics coumarin molecules with unusual solution and solid dual efficient luminescence

3-Imidazolyl coumarin molecules were synthesized under solvent-free condition and the optical properties both in solution and the solid state were determined. The compounds showed dual efficient luminescence, which were blue fluorescence with the highest fluorescence quantum yield being more than 0.9 and also exhibited favorable yellow solid-state fluorescence. Additionally, by using density functional theory (DFT) and time-dependent DFT (TD-DFT) calculation, all structures were optimized and the associated optical performances showed similar results as the experimental results.     

Synthesis and properties of novel calix[4]arene derivatives bearing fluorogenic coumarin units

Four novel calix[4]arene derivatives 5-8 bearing four fluorogenic coumarin units attached via imino group acting also as binding sites at the upper rim have been prepared and characterized by IR, IH NMR and MS. Compounds 5-8 adopt a cone conformation. Their complexation properties to different heavy and transition metal ions have been studied by UV-vis spectroscopy. Compounds 5, 6, 8 show selective recognition to Fe^3＋ and Cr^3＋.     

Bimane fluorogenic substrates for microdetermination of angiotensin converting enzyme level in serum.

The fluorescence of 9,10-dioxa-syn-3,4,6,7-tetramethylbimane (bimane) was found to be quenched in the presence of nitrated aromatic amino acid. Bimane peptides containing nitrated amino acid (1a, b) were shown to be useful fluorogenic substrates for the assay of angiotensin I converting enzyme (ACE) from rabbit lung, similar to bimane substrate containing tryptophan (3) previously reported. Among these bimane substrates, substrate 3 was shown to be a potent fluorogenic substrate for microdetermination of the ACE level in human serum.     

Design and synthesis of a dual linker for solid phase synthesis of oleanolic acid derivatives

A hydrophilic amino-terminated poly(ethylene glycol)-type dual linker for solid phase synthesis of oleanolic acid derivatives using trityl chloride resin was designed and synthesized for the first time. Model reactions in both liquid and solid phase were performed to show the feasibility of its selective cleavage at two different sites. The biological assay results indicated that the long and flexible alkyl ether functionality in the linker is less likely to be critical for the binding event. Following the successful solid-phase synthesis of model compounds, the potential of this dual linker in reaction monitoring and target identification is deemed worthy of further study.     

Zirconyl chloride promoted highly efficient solid phase synthesis of amide derivatives

An efficient solid phase route for the synthesis of amide derivatives by the reaction of carboxylic acids with urea in the presence of catalytic amount of zirconyl chloride under microwave irradiation conditions was described.In this way,a range of interesting amide derivatives was obtained in good to excellent yields.The catalyst was recycled with fresh reactants and it gave almost similar results without significant loss of activity up to the third run.     

A solid phase linker strategy for the direct synthesis of EDANS-labelled peptide substrates

A novel linker strategy for the efficient synthesis of peptides C-terminally labelled with the EDANS fluorophore is described. Using this support, FRET peptide substrates bearing EDANS/Dabcyl fluorescent donor/acceptor groups can be readily prepared using standard Fmoc solid phase methods.     

Microwave-assisted synthesis and antioxidant properties of hydrazinyl thiazolyl coumarin derivatives

ABSTRACT: Coumarin derivatives exhibit a wide range of biological properties including promising antioxidant activity. Furthermore, microwave-assisted organic synthesis has delivered rapid routes to N- and O-containing heterocycles, including coumarins and thiazoles. Combining these features, the use of microwave-assisted processes will provide rapid access to a targeted coumarin library bearing a hydrazino pharmacophore for evaluation of antioxidant properties. RESULTS: Microwave irradiation promoted 3 of the 4 steps in a rapid, convergent synthesis of a small library of hydrazinyl thiazolyl coumarin derivatives, all of which exhibited significant antioxidant activity comparable to that of the natural antioxidant quercetin, as established by DPPH and ABTS radical assays. CONCLUSIONS: Microwave dielectric heating provides a rapid and expedient route to a series of hydrazinyl thiazolyl coumarins to investigate their radical scavenging properties. Given their favourable properties, in comparison with known antioxidants, these coumarin derivatives are promising leads for further development and optimization.     

A new efficient enantioselective synthesis of malonylphenylalanyl and malonylmethylphenylalanyl derivatives suitable for solid phase peptide synthesis

A new synthesis of enantiomerically pure malonylphenylalanyl and malonylmethylphenylalanyl derivatives was developed in which the corresponding prochiral enamides were treated by asymmetric hydrogenation using the Rh(I)-(S,S)-Me-DuPHOS system. These unnatural amino acids were suitably protected and can be used in solid phase peptide synthesis.     

无溶剂条件下离子液体催化香豆素衍生物的绿色合成(英文)

Brnsted acidic ionic liquids, namely 2-pyrrolidonium hydrogen sulfate, N-methyl-2-pyrrolidonium hydrogen sulfate, N-methyl-2-pyrrolidonium dihydrogen phosphate, (4-sulfobutyl)tris(4-sulfophenyl)phosphonium hydrogen sulfate, and triphenyl(propyl-3-sulfonyl)phosphonium toluenesulfonate, catalyzed efficient Pechmann condensation of phloroglucinol with β-keto ethyl/ methyl esters. 5,7-Dihydroxy-4-methylcoumarin and 5,7-dihydroxy-4-phenylcoumarin were prepared in good to excellent yields under mild, ambient, and solvent-free conditions. Pyrano[2,3-h] coumarins were then prepared by one-pot three-component reactions of 5,7-dihydroxy-4-subsituted coumarin, malononitrile, and aldehydes in the presence of catalytic amounts of Br nsted basic ionic liquids, namely 2-hydroxyethylammonium formate, 3-hydroxypropanaminium acetate, 1-butyl-3-methylimidazolium hydroxide, pyrrolidinium formate, and pyrrolidinium acetate, under thermal solvent-free conditions. The catalysts are environmentally benign and can be easily prepared, stored, and recovered without significant loss of activity.     

A solid phase library synthesis of hydroxyindoline-derived tricyclic derivatives by Mitsunobu approach

Hydroxyindoline-derived scaffold, 9, was synthesized with the goal of generating a library of indoline-based natural product-like tricyclic derivatives to be utilized as small-molecule chemical probes. The tricyclic ring was obtained by a Mitsunobu reaction of the N-nosyl amino acid conjugate with the primary hydroxyl group. The solid-phase synthesis was achieved by immobilizing scaffold 9 onto the solid support giving a compound, 15. This was then subjected to a series of reactions on solid phase, including the Mitsunobu reaction, leading to the desired indoline-derived tricyclic derivative. The final product has two diversity sites: (i) amino acid as the first diversity and (ii) amidation of the secondary amine for the second diversity. These two diversity sites were utilized in the library generation by IRORI split-and-mix approach.     

Optimization of spiroimidazolidinone derivatives synthesis on solid phase using SynPhase™ Lanterns

We report the synthesis of 1,4,8-triazaspiro[4.5]decan-2-one derivatives from N-benzyl-4-piperidone and N-protected amino acid amides on solid support. We have translated the chemistry from solution to solid phase using a backbone amide linker (BAL) mimic. Using a parallel combinatorial approach, we performed the optimization of the synthesis on SynPhase™ Lanterns.     

Novel UV-sensitive bis-chalcone derivatives: synthesis and photocrosslinking properties in solution and solid PMMA film

A series of chalcone derivatives in which two chalcone groups are attached by alkyldioxy chains were synthesized and characterized by ¹H NMR, UV–Vis, and Fourier transform infrared (FTIR) spectral analysis. Upon the irradiation of 365-nm UV light, the chalcone groups in the molecules underwent [2π + 2π] photodimerization. The photocrosslinking properties were investigated both in solution and in polymethyl methacrylate (PMMA) solid films on quartz plate. It has been found that the photocrosslinking rates of the compounds depended on the different flexibility of the functional groups, which was determined by the length of the spacer chain between the two chalcone moieties. The longest soft chain containing derivatives has a faster photocrosslinking rate both in solution and in solid film. Irradiated by polarized ultraviolet light (PUV), all of the films doped with bis-chalcone derivatives showed an anisotropic absorption property, which may give a promising application as LC-alignment materials.